Mary Riddoch (1901-1966), an extraordinary tale of survival.

In 1934 Mary Riddoch sustained a traumatic spinal injury as a result of a road traffic accident. Although a few surviving servicemen from the First World War have been recorded, this is the first account of a female paraplegic patient surviving a traumatic spinal injury. Her personal circumstances greatly contributed to her long survival: she was a qualified doctor, she was the sister of George Riddoch the neurologist who treated soldiers who had sustained spinal cord injuries during the First World War, and she was fortunate to have benefited from the dedicated care of nurse Dorothy Fiddes. Her great-nephew, Graeme Riddoch, is one of the authors of this paper and his recollections provide a unique perspective to this case report.

The combined oral contraceptive pill. A practical review of current options.

BACKGROUND: The last decade has seen an increase in the number of combined oral contraceptive pills available in Australia, and thereby the number of options available to the patient and prescriber. OBJECTIVE: This article will deal with day to day problems related to, and the special circumstances for prescribing of oral contraception in general practice. DISCUSSION: The range of products available and their varying advantages and disadvantages allows the tailoring of prescriptions to suit individual needs.

Tasmanian survey of pill symptoms.

OBJECTIVE: To investigate young women who were currently using oral contraceptives with respect to their satisfaction, side effects, understanding of long term benefits and anxieties. METHOD: The survey was completed by 227 attendees at Family Planning Tasmania who completed a survey questionnaire during their visit. RESULTS: Seventy-eight per cent of respondents were 'very happy' or 'happy' with oral contraceptives. Overall the group reported shorter, lighter and less painful periods when compared prior to pill use, with slight increase in breast swelling and tenderness as well as fluid retention. Overall there was weight gain more often than weight loss during pill use. There was very poor understanding of the long term benefits of pill use. DISCUSSION: Although oral contraceptives are the most effective form of contraceptive, many women discontinue their use because of side effects. If women are warned about these possible effects, they may be more prepared to tolerate them. However, there is very little objective data available on the incidence of various effects on Australian women. This study shows that the single most important side effect reported was weight gain, and that we recommend that women be counselled about diet when commencing the pill. There also needs to be education about the numerous beneficial long term effects of oral contraceptive use.

Inadvertent pregnancies in oral contraceptive users.

Two hundred and nine inadvertent pregnancies in oral contraceptive users were studied to determine the associated factors. The percentage of Pill types also were compared with the market usage over the same period. We found that the classically-suggested cofactors, such as missed pills, late pills, drug ingestion, and gastrointestinal upsets were reported commonly. The triphasic Pills also were represented more frequently than would have been expected from their share of the market.

PIP: Although oral contraceptives (OCs) are the most effective form of reversible fertility control, inadvertent pregnancies do occur in OC users. The most common causes of these pregnancies seem to be missed pills, drug interactions, and malabsorption resulting from vomiting or diarrhea. To assess the relative importance of these causes, a pilot study was conducted at family planning centers in Australia. In response to a questionnaire, 12 centers reported 209 cases of OC-associated inadvertent pregnancy occurring between December 1985 and July 1986. Triphasic OCs were used by 52% of these women, while only 42% of Australian women overall use this type of formulation. 35% of women with inadvertent pregnancies reported they had missed taking pills; another 25% had taken a pill late (at least 36 hours after the previous tablet). 34% of these women had used drugs believed to interact with OCs in their last 2 cycles before conception. In the majority of these cases (67%), these were antibiotic agents--most often amoxicillin. 27% reported vomiting or diarrhea in association with OC failure. Finally, 22% of the women had suffered some form of illness (various respiratory, urinary, and gastrointestinal infections) since the last menstrual cycle. 16% of the women experienced breakthrough bleeding in the cycle in which conception occurred. No predisposing factors could be identified in 14% of the women with unintended pregnancies. The most significant finding of this study is the higher rate of inadvertent pregnancies among users of triphasic as opposed to monophasic OCs. Also confirmed were the well-recognized risks of missed pills, late pills, drug interactions, and diarrhea and vomiting. OC users should be advised to take additional contraceptive precautions until at least 7 consecutive tablets have been taken after an episode that may impair the efficacy of the pill.

Metallothionein immunoreactivity in the liver and kidney of copper injected rats.

Adult male rats were injected intraperitoneally with copper sulphate in physiological saline (3 mg copper/kg body wt). Metallothionein-I (MT-I) levels in liver, kidney, plasma and red blood cells were measured by radioimmunoassay (RIA), prior to the injection and after 7, 16 and 24 h. Copper and zinc levels in liver and kidneys were also monitored. Concentrations of MT-I in liver and kidneys showed a rapid increase and remained elevated for 24 h. Copper concentrations also increased in both tissues but zinc levels remained constant in the kidney and rose only slightly in the liver. MT-I levels increased gradually in plasma but decreased in the red blood cells. Immunochemistry of liver and kidney, using the direct peroxidase technique with antiserum to rat MT-I, revealed an increase in staining in both tissues after copper administration, consistent with the RIA results. The change in distribution of immunoreactive material with time after copper injection indicates a role for MT in the sequestration and excretion of copper in acutely loaded animals.

Neuropeptide Y (NPY) innervation of the ovine pineal gland.

A dense network of neuropeptide Y (NPY)-like immunoreactive (NPY-LI) fibres was revealed in the ovine pineal gland at the light microscope level. The dorsal and peripheral regions of the gland contained the most dense concentration of NPY-LI fibres with relatively few fibres in the mid-region and almost none in the pineal stalk. The effect of NPY in conjunction with isoproterenol (ISO) on cyclic AMP (cAMP) accumulation and noradrenaline (NA) on melatonin synthesis was investigated using in vitro techniques. NPY had no effect on the stimulation of cAMP or melatonin synthesis by the adrenergic agonists.

Autoradiographic studies of the renal clearance of circulating type I collagen fragments in the rat.

Cyanogen bromide (CNBr) peptides of [3H]-labelled type I collagen isolated from young rat skin were injected into adult rats via the tail vein. After 1, 5 and 10 minutes, the fate of the circulating radioactive peptides was investigated by measurement of the tissue distribution of radioactivity. Rapid removal of peptides from the circulation and their concomitant accumulation in the kidney proximal tubule epithelia was confirmed by autoradiography of kidney sections at the light microscope level. Immunopositive material was also identified and localized in proximal tubules using antibodies directed against denatured type I collagen chains and their CNBr degradation products. Ultrastructural autoradiography indicated that rapid removal of collagen peptides from the glomerular filtrate occurs via the brush border, apical vacuoles, and lysosomes.

Adrenergic and VIP stimulation of cyclic AMP accumulation in ovine pineals.

In vitro autoradiography of [125I]cyanopindolol ([125I]cyp) binding to sections of ovine pineal reveals a uniform distribution of beta-adrenergic receptors throughout the gland. Norepinephrine (NE) stimulated cyclic AMP production in pineal slices in both a time- and dose-dependent manner, producing a maximal two-fold increase. NE, isoproterenol (ISO) and epinephrine (E) stimulate cyclic AMP (cAMP) production with equal potency. NE stimulation of cAMP was totally blocked by propranolol (beta antagonist) but only partially blocked by practolol (a beta 1 preferential antagonist) indicating a mixed population of beta 1 and beta 2 receptor subtypes. Displacement of [125I]cyp binding by either practolol or zinterol (preferential beta 2 agonist) revealed IC50s of 1.3 x 10(-5) M and 9.95 x 10(-8) M respectively, confirming a mixed population of beta 1 and beta 2 receptors. A range of peptides previously localised within the pineal by immunocytochemistry were tested at a concentration of 10(-5) M for their effect on cyclic AMP production in pineal homogenates. Only vasoactive intestinal peptide (VIP) was effective showing a dose-dependent stimulation. ISO and VIP stimulation of cAMP were additive indicating action via independent receptors.

Stimulation of melatonin synthesis in ovine pineals in vitro.

Static and superfused pineal slices (750 micron) have been used to study the control of melatonin synthesis by ovine pineals. Static incubates show a time-dependent accumulation of melatonin in the medium; this is significantly increased by stimulation with norepinephrine (NE) (10(-5) M), reaching 300% above control levels after 4 h. Perifused pineal slices show a rapid rise in melatonin release within 12-18 min in response to NE stimulation. This reaches a 3.5-4.5-fold increase in melatonin released within 30 min. Withdrawal of NE is associated with a rapid return to prestimulated levels within 12-18 min. These time-course characteristics compare favorably to those changes seen in vivo. The formation of [14C]melatonin from [14C]-tryptophan shows a linear increase with time. In the presence of NE (10(-5) M), the rate of synthesis is increased, albeit after an initial time lag of at least 30 min. The latter may reflect an N-acetyltransferase-independent mechanism of synthesis and release. In static incubations, propranolol (10(-5) M) inhibited NE-induced melatonin production by about 60%, but prazosin (10(-5) M) had no effect. As dibutyryl cyclic AMP (10(-3) M) stimulated melatonin production, it is concluded that beta-receptors are of primary importance to the control of melatonin production, as in the rat. The role of alpha 1-receptors is less clear, but the stimulatory action of phorbol 12-myristate 13-acetate on melatonin release implicates a receptor linked to phosphatidylinositol turnover.

Kidney lesions in copper-deficient rats.

Rats fed a diet deficient in copper were found, in comparison to control rats, to have lesions in the cortex, medulla and papilla of the kidney. Within the cortex, the lesions consisted of mild atrophy of the convoluted tubules, thickening of their basement membranes and fragmentation of the reticulin framework. In the medulla and papilla, selected zones of the loop of Henle were disorganized, with their epithelia appearing atrophied and their basement membranes fragmented and irregular. The epithelial cells of the collecting tubules were atrophied and vacuolated and their basement membranes thickened. Throughout the kidney, blood vessels were distented and engorged with large numbers of erythrocytes. The most likely explanation for these lesions is vascular underperfusion which could be due to a primary effect of copper deficiency on the kidney or could be secondary to the other cardiovascular lesions that are known to occur in copper deficiency.

Evidence for renal tubular resorption of collagen fragments from immunostaining of rat kidney with antibodies specific for denatured type I collagen.

Antibodies to rat collagens I and III were raised in sheep. The antisera to collagen I were separated by affinity chromatography into components specific for either native or denatured forms. Immunolabelling of rat kidney sections with antibodies to native collagen I showed staining only of the interstitial matrix. By contrast, antibodies to denatured collagen I revealed the presence of immunoreactive material primarily in the upper part of the proximal tubules, detected in both fixed and cryostat sections. In fixed material, the granular appearance of staining in the region of the brush border was shown to be distinct from the protein droplets counterstained by toluidine blue. Collagen III antibodies stained the interstitial matrix in a similar pattern to that for native collagen I, but no proximal tubule staining was observed despite the fact that antibodies to denatured collagen III were shown to be present. No material reactive with denatured collagen I antibodies was detected in urine or serum by an inhibition ELISA technique. The results are discussed in terms of renal tubular resorption of collagen degradation products.

Immunocytochemical staining of rat tissues with antibodies to denatured type I collagen: a technique for localizing areas of collagen degradation.

Sheep were immunized with purified native collagen I and the antisera were fractionated by affinity chromatography on columns containing either native or heat-denatured forms of the antigen. Crossed immunoadsorption ensured complete removal of antibodies to terminal, non-helical regions resulting in antibodies that were specific for either native or central, non-helical determinants, as judged by ELISA and immunoblotting. Tissue immunostaining showed some areas, such as duodenal villus and blood vessels, where staining with antibodies against native and denatured collagen gave similar patterns, but other areas, such as pancreas, where immunolocalization of native collagen I was not accompanied by similar detection of the denatured form. Immunodetection on tissue sections of added human fibronectin showed similar staining patterns to those for denatured collagen. Areas of tissue showing the presence of denatured collagen were interpreted as an indication of collagen degradation, and the technique may therefore provide a means of assessing the pattern of collagen turnover within individual tissues.